Liver Tumors

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Focused ultrasound is cleared to treat liver tumors in the United States.

The US Food and Drug Administration (FDA) has cleared HistoSonics’ novel therapy platform – called EdisonTM – to treat liver tumors. EdisonTM uses histotripsy to noninvasively destroy tissue in the liver and is the first and only such platform available in the US. This is also the first time the use of histotripsy has earned regulatory approval worldwide. Read More

Focused Ultrasound Therapy

Focused ultrasound is a rapidly evolving, noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with liver tumors. This novel technology focuses beams of ultrasound energy precisely and accurately on targets deep in the body without damaging surrounding normal tissue.

How it Works
Where the beams converge, focused ultrasound produces several therapeutic effects that are being evaluated.

One mechanism is the production of precise ablation (thermal destruction of tissue). This destruction can be done to completely destroy the target or to partially treat it, and partial treatment is believed to stimulate the patient’s immune response, which may have a broader impact. 

Another mechanism is the use of mechanical (non-thermal) histotripsy to destroy the tumor. 

A third mechanism is to use focused ultrasound to cause hyperthermia which enables the local release and absorption of a therapeutic that is contained in the blood stream. 

Advantages
The primary options for treatment of liver tumors include surgery, chemotherapy, radiotherapy, localized destruction of the tumor tissue (via radiofrequency ablation, alcohol injection, cryosurgery, or laser photocoagulation), or combination of two or more of these options. The long-term solution for primary liver cancer is often liver transplantation.

For certain patients, focused ultrasound could provide a noninvasive alternative to surgery with less risk of complications – such as surgical wound healing or infection – at a lower cost. It can reach the desired target without damaging surrounding tissue and is repeatable, if necessary. Focused ultrasound can also enhance the chemotherapy dose for the target, with less impact to the rest of the patient. 

Clinical Trials

A clinical trial in the UK is recruiting patients with colorectal cancer and metastasis to the liver. It uses focused ultrasound to activate a microbubble preparation designed to improve the penetration of chemotherapy to the liver.  

A clinical trial is using heat sensitive chemotherapy and focused ultrasound to treat relapsing solid tumors.  

For a full list of clinical trials, please click here.

See a list of treatment sites > 
See a list of laboratory research sites >

Regulatory Approval and Reimbursement

In October 2023, the US Food and Drug Administration cleared HistoSonics’ Edison device to noninvasively treat liver tumors using histotripsy. 

A focused ultrasound system has been approved in China, Russia, Europe, and Korea for treatment of liver cancer.

To the best of our knowledge, the use of focused ultrasound to treat liver cancer is not yet widely reimbursed by medical insurance.

Notable Papers

Yeats E, Lu N, Stocker G, Komaiha M, Sukovich JR, Xu Z, Hall TL. In Vivo Cavitation-Based Aberration Correction of Histotripsy in Porcine Liver. IEEE Trans Ultrason Ferroelectr Freq Control. 2024 Aug;71(8):1019-1029. doi: 10.1109/TUFFC.2024.3409638. Epub 2024 Aug 19. PMID: 38837932 

Sandilos G, Butchy MV, Koneru M, Gongalla S, Sensenig R, Hong YK. Histotripsy – hype or hope? Review of innovation and future implications. J Gastrointest Surg. 2024 Aug;28(8):1370-1375. doi: 10.1016/j.gassur.2024.05.038. Epub 2024 Jun 9. PMID: 38862075 

Lari S, Kohandel M, Kwon HJ. Model based deep learning method for focused ultrasound pathway scanning. Sci Rep. 2024 Aug 29;14(1):20042. doi: 10.1038/s41598-024-70689-9. PMID: 39198623 

Yang X, Liao Y, Fan L, Lin B, Li J, Wu D, Liao D, Yuan L, Liu J, Gao F, Feng G, Du X. High-intensity focused ultrasound ablation combined with immunotherapy for treating liver metastases: A prospective non-randomized trial. PLoS One. 2024 Jul 5;19(7):e0306595. doi: 10.1371/journal.pone.0306595. eCollection 2024. PMID: 38968190 

Han M, Song W, Lei K, Cai B, Qin D. Ultrasonic Nakagami imaging for automatically positioning and identifying the treated lesion induced by histotripsy. Ultrason Sonochem. 2024 Jul 25:107002. doi: 10.1016/j.ultsonch.2024.107002. PMID: 39084943 

Iqbal MF, Shafique MA, Abdur Raqib M, Fadlalla Ahmad TK, Haseeb A, M A Mhjoob A, Raja A. Histotripsy: an innovative approach for minimally invasive tumour and disease treatment. Ann Med Surg (Lond). 2024 Mar 5;86(4):2081-2087. doi: 10.1097/MS9.0000000000001897. eCollection 2024 Apr. PMID: 38576932 

Xu Z, Khokhlova TD, Cho CS, Khokhlova VA. Histotripsy: A Method for Mechanical Tissue Ablation with Ultrasound. Annu Rev Biomed Eng. 2024 Feb 12. doi: 10.1146/annurev-bioeng-073123-022334. PMID: 38346277 

Simon A, Edsall C, Maxwell A, Vlaisavljevich E. Effects of pulse repetition frequency on bubble cloud characteristics and ablation in single-cycle histotripsy. Phys Med Biol. 2024 Jan 12;69(2). doi: 10.1088/1361-6560/ad11a1. PMID: 38041873 

Worlikar T, Hall T, Zhang M, Mendiratta-Lala M, Green M, Cho CS, Xu Z. Insights from in vivo preclinical cancer studies with histotripsy. Int J Hyperthermia. 2024;41(1):2297650. doi: 10.1080/02656736.2023.2297650. Epub 2024 Jan 12. PMID: 38214171 

Ashida R, Kawabata KI, Asami R, Kitano M. Novel treatment system using endoscopic ultrasound-guided high-intensity focused ultrasound: A proof-of-concept study. Pancreatology. 2024 Feb;24(1):88-92. doi: 10.1016/j.pan.2023.11.013. Epub 2023 Nov 21. PMID: 38036413 

Wade R, South E, Anwer S, Sharif-Hurst S, Harden M, Fulbright H, Hodgson R, Dias S, Simmonds M, Rowe I, Thornton P, Eastwood A. Ablative and non-surgical therapies for early and very early hepatocellular carcinoma: a systematic review and network meta-analysis. Health Technol Assess. 2023 Dec;27(29):1-172. doi: 10.3310/GK5221. PMID: 38149643 

Liu Y, Zhang Y, Du D, Gu X, Zhang X, Hong G, Lai X. Nanotargeted Cationic Lipid Microbubbles Carrying HSV-TK Gene Inhibit the Development of Subcutaneous Liver Tumor Model After HIFU Ablation. J Ultrasound Med. 2024 Jan;43(1):95-107. doi: 10.1002/jum.16342. Epub 2023 Oct 10. PMID: 37815381 

Guo X, Lin J, Pan L, He K, Huang Z, Chen J, Lin C, Zeng B, Luo S, Wang M. Ultrasound-triggered release of miR-199a-3p from liposome nanobubbles for enhanced hepatocellular carcinoma treatment. Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):560-571. doi: 10.1080/21691401.2023.2268137. Epub 2023 Oct 18. PMID: 37850395 

Zhou H, Li F, Luo L, Xiong X, Zhou K, Zhu H, Zhang J, Li P. Safety of Sonazoid in Assisting High-Intensity Focused Ultrasound Ablation Therapy for Advanced Liver Malignant Lesions: A Single-Arm Clinical Study. Ultrasound Med Biol. 2024 Jan;50(1):134-141. doi: 10.1016/j.ultrasmedbio.2023.09.014. Epub 2023 Oct 19. PMID: 37865612 

Dalzell CG, Taylor AC, White SB. New Insights on Liver-Directed Therapies in Hepatocellular Carcinoma. Cancers (Basel). 2023 Dec 8;15(24):5749. doi: 10.3390/cancers15245749. PMID: 38136295 

Tang F, Zhong Q, Ni T, Xue Y, Wu J, Deng R, Zhang Q, Li Y, He X, Yang Z, Zhang Y. High-intensity focused ultrasound ablation combined with systemic therapy for unresectable colorectal cancer liver metastasis: A propensity score-matched analysis. Cancer Med. 2023 Nov 30. doi: 10.1002/cam4.6774. PMID: 38032013 

Li H, He H, Tang J, Luo T, Yang G, Huang L, Dong X, Liu Z. A new sonoablation using acoustic droplet vaporization and focused ultrasound: A feasibility study. Med Phys. 2023 Nov;50(11):6663-6672. doi: 10.1002/mp.16742. Epub 2023 Sep 20. PMID: 37731063 

Dupré A, Rivoire M, Metzger S, Cropet C, Vincenot J, Peyrat P, Chen Y, Pérol D, Melodelima D. Intra-operative High-Intensity Focused Ultrasound in Patients With Colorectal Liver Metastases: A Prospective Ablate-and-Resect Study. Ultrasound Med Biol. 2023 Aug;49(8):1845-1851. doi: 10.1016/j.ultrasmedbio.2023.04.010. Epub 2023 May 31. PMID: 37268553 

Haram M, Hansen R, Bouget D, Myhre OF, Davies CL, Hofsli E. Treatment of Liver Metastases With Focused Ultrasound and Microbubbles in Patients With Colorectal Cancer Receiving Chemotherapy. Ultrasound Med Biol. 2023 Sep;49(9):2081-2088. doi: 10.1016/j.ultrasmedbio.2023.05.013. Epub 2023 Jun 17. PMID: 37336691 

Lorton O, Guillemin PC, Peloso A, M’Rad Y, Crowe LA, Koessler T, Poletti PA, Boudabbous S, Ricoeur A, Salomir R. In Vivo Thermal Ablation of Deep Intrahepatic Targets Using a Super-Convergent MRgHIFU Applicator and a Pseudo-Tumor Model. Cancers (Basel). 2023 Aug 3;15(15):3961. doi: 10.3390/cancers15153961. PMID: 37568777 

Wang YB, Zeng HS, Salameen H, Miao CM, Chen L, Ding X. High-intensity focused ultrasound versus transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis. Int J Radiat Biol. 2023 Jul 31:1-11. doi: 10.1080/09553002.2023.2232009. PMID: 37523652  

Liao M, Chen F, Chen L, Wu Z, Huang J, Pang H, Cheng C, Wu Z, Ma L, Lu Q. Synergistic Enzyme-Mimetic Catalysis-Based Non-Thermal Sonocavitation and Sonodynamic Therapy for Efficient Hypoxia Relief and Cancer Ablation. Small. 2023 Jun 15:e2302744. doi: 10.1002/smll.202302744. PMID: 37322373  

Haram M, Hansen R, Bouget D, Myhre OF, Davies CL, Hofsli E. Treatment of Liver Metastases With Focused Ultrasound and Microbubbles in Patients With Colorectal Cancer Receiving Chemotherapy. Ultrasound Med Biol. 2023 Jun 17:S0301-5629(23)00171-0. doi: 10.1016/j.ultrasmedbio.2023.05.013. PMID: 37336691  

Wang J, Wan L, Huang G, Chen C, Wu Y. Comparison of high-intensity focused ultrasound and microwave ablation for the treatment of small liver metastatic tumors. J Int Med Res. 2023 Apr;51(4):3000605231165551. doi: 10.1177/03000605231165551. 

Zou YW, Ren ZG, Sun Y, Liu ZG, Hu XB, Wang HY, Yu ZJ. The latest research progress on minimally invasive treatments for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2023 Feb;22(1):54-63. doi: 10.1016/j.hbpd.2022.08.004. Epub 2022 Aug 19. 

Wah TM, Pech M, Thormann M, Serres X, Littler P, Stenberg B, Lenton J, Smith J, Wiggermann P, Planert M, Vidal-Jove J, Torzilli G, Solbiati L. A Multi-centre, Single Arm, Non-randomized, Prospective European Trial to Evaluate the Safety and Efficacy of the HistoSonics System in the Treatment of Primary and Metastatic Liver Cancers (#HOPE4LIVER). Cardiovasc Intervent Radiol. 2023 Feb;46(2):259-267. doi: 10.1007/s00270-022-03309-6. Epub 2022 Nov 15. 

Mauch SC, Zlevor AM, Knott EA, Couillard AB, Periyasamy S, Williams EC, Swietlik JF, Laeseke PF, Zhang X, Xu Z, Abel EJ, Lee FT Jr, Ziemlewicz TJ. Hepatic and Renal Histotripsy in an Anticoagulated Porcine Model. J Vasc Interv Radiol. 2023 Mar;34(3):386-394.e2. doi: 10.1016/j.jvir.2022.11.034. Epub 2022 Dec 9. 

Xiao C, Liu S, Ge G, Jiang H, Wang L, Chen Q, Jin C, Mo J, Li J, Wang K, Zhang Q, Zhou J. Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies. Front Pharmacol. 2023 Feb 6;14:1086813. doi: 10.3389/fphar.2023.1086813. eCollection 2023. 

Froghi S, de Andrade MO, Hadi LM, Gelat P, Rashidi H, Quaglia A, Fuller B, Saffari N, Davidson B. Liver Ultrasound Histotripsy: Novel Analysis of the Histotripsy Site Cell Constituents with Implications for Histotripsy Application in Cell Transplantation and Cancer Therapy. Bioengineering (Basel). 2023 Feb 20;10(2):276. doi: 10.3390/bioengineering10020276. 

Robinson TP, Pebror T, Krosin ME, Koniaris LG. Ablative Therapy in Non-HCC Liver Malignancy. Cancers (Basel). 2023 Feb 14;15(4):1200. doi: 10.3390/cancers15041200. 

Cambronero S, Dupré A, Mastier C, Melodelima D. Non-invasive High-Intensity Focused Ultrasound Treatment of Liver Tissues in an In Vivo Porcine Model: Fast, Large and Safe Ablations Using a Toroidal Transducer. Ultrasound Med Biol. 2023 Jan;49(1):212-224. doi: 10.1016/j.ultrasmedbio.2022.08.015. Epub 2022 Oct 28. 

Elfatairy K. First-In-Human Histotripsy Trial for Liver Tumor Treatment: The New Echo Superpower. Radiol Imaging Cancer. 2023 Jan;5(1):e229026. doi: 10.1148/rycan.229026. 

Tang X, He X, Jiang H.Efficacy and safety of HIFU in combination with TACE in unresectable pediatric HB: A randomized, controlled, single-center clinical trial. Medicine (Baltimore). 2022 Dec 2;101(48):e32022. doi: 10.1097/MD.0000000000032022. 

Guntur SR, Kim SC, Choi MJ. A Cost-Effective Reusable Tissue Mimicking Phantom for High Intensity Focused Ultrasonic Liver Surgery. Bioengineering (Basel). 2022 Dec 9;9(12):786. doi: 10.3390/bioengineering9120786. 

Zou X, Li T, Mao Y, Zhu M, Chen X, Niu J, Dong T, Jiang J, Yang X. Multifunctional Drug-Loaded Phase-Change Nanoparticles Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Affecting the Activity of Activated Hepatic Stellate Cells. Biomed Res Int. 2022 Nov 12;2022:6441179. doi: 10.1155/2022/6441179. eCollection 2022. 

Knott EA, Zlevor AM, Hinshaw JL, Laeseke PF, Longhurst C, Frank J, Bradley CW, Couillard AB, Rossebo AE, Xu Z, Lee FT Jr, Ziemlewicz TJ. A comparison study of microwave ablation vs. histotripsy for focal liver treatments in a swine model. Eur Radiol. 2022 Sep 1. doi: 10.1007/s00330-022-09112-8. 

Shi S, Li H, Zheng X, Lv L, Liao S, Lu P, Liu M, Zhao H, Mei Z. Visualization system based on hierarchical targeting for diagnosis and treatment of hepatocellular carcinoma. Mater Today Bio. 2022 Aug 22;16:100398. doi: 10.1016/j.mtbio.2022.100398. eCollection 2022 Dec. 

Heo J, Joung C, Pahk K, Pahk KJ. Investigation of the long-term healing response of the liver to boiling histotripsy treatment in vivo. Sci Rep. 2022 Aug 24;12(1):14462. doi: 10.1038/s41598-022-18544-7. 

Zhang L, Qiao L, Zhang M, Xue Y, Zhang X, Gao X. Comparison of prognosis among patients with colorectal cancer liver metastases treated by surgical resection, radiofrequency ablation and HIFU: A protocol for network meta-analysis. Medicine (Baltimore). 2022 Aug 19;101(33):e27915. doi: 10.1097/MD.0000000000027915. 

Finotti M, Romano M, Brizzolari M, Scopelliti M, Zanus G. Comment on: “A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis”. Hepatobiliary Surg Nutr. 2022 Aug;11(4):640-642. doi: 10.21037/hbsn-22-202. 

Ozen M, Raissi D. Editorial comment: a review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis. Hepatobiliary Surg Nutr. 2022 Jun;11(3):453-456. doi: 10.21037/hbsn-22-138. 

Zhang JY, Chen L, Ma R, Miao CM, Wang YB. Effectiveness and safety of focused ultrasound ablation surgery compared with radiofrequency ablation in primary hepatocellular carcinoma treatment: a meta-analysis. Transl Cancer Res. 2021 May;10(5):2080-2090. doi: 10.21037/tcr-20-3458. 

Tsang SH, Ma KW, She WH, Chu F, Lau V, Lam SW, Cheung TT, Lo CM. High-intensity focused ultrasound ablation of liver tumors in difficult locations. Int J Hyperthermia. 2021 Sep;38(2):56-64. doi: 10.1080/02656736.2021.1933217. 

Merrill R, Odéen H, Dillon C, Bitton R, Ghanouni P, Payne A. Design and evaluation of an open-source, conformable skin-cooling system for body magnetic resonance guided focused ultrasound treatments. Int J Hyperthermia. 2021;38(1):679-690. doi: 10.1080/02656736.2021.1914872. 

Barrere V, Sanchez M, Cambronero S, Dupré A, Rivoire M, Melodelima D. Evaluation of Ultrasonic Attenuation in Primary and Secondary Human Liver Tumors and Its Potential Effect on High-Intensity Focused Ultrasound Treatment. Ultrasound Med Biol. 2021 Apr 21:S0301-5629(21)00135-6. doi: 10.1016/j.ultrasmedbio.2021.03.014. 

Hendricks A, Weber P, Simon A, Saunier S, Coutermarsh-Ott S, Grider D, Jove JV, Allen IC, Luyimbazi D, Vlaisavljevich E. Histotripsy for the Treatment of Cholangiocarcinoma Liver Tumors: In Vivo Feasibility and Ex Vivo Dosimetry Study. IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Apr 15;PP. doi: 10.1109/TUFFC.2021.3073563. 

Gu L, Shen Z, Ji L, Ng DM, Du N, He N, Fan X, Yan K, Zheng Z, Chen B, Ma L, Qiu G, Chen P, Zheng J, Yang T. High-intensity focused ultrasound alone or combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with unsuitable indications for hepatectomy and radiofrequency ablation: a phase II clinical trial. Surg Endosc. 2021 Mar 31. doi: 10.1007/s00464-021-08465-3. 

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